Non-healing ischemic wounds are a major problem for Veterans with physical impairment and/or disability. These chronic wounds cause significant pain and disability and occur at an alarmingly high frequency in at-risk Veteran populations cared for by the Veterans Healthcare Administration (VHA). The use of electrical stimulation (ES) for ischemic wound therapy has long been known but the outcomes have been variable. In previous work we developed an untethered electronic bandage with all the components of a surface stimulation system mounted on a flexible substrate. We systematically investigated the effects of a range of clinically relevant ES and found two paradigms that significantly enhanced healing in a rat ischemic wound model. One of these paradigms was also found to significantly reduce wound infection in an acute preclinical model of clinically relevant large wounds. The project will provide translational development and testing in a relevant large animal model of the Smart Modular Adaptive Electrotherapy Delivery System (SmartMAEDS) to provide both treatment and remote monitoring of chronic ischemic wounds. The patented SmartMAEDS system is an innovative approach incorporating both ES and real-time wound monitoring. SmartMAEDS will reduce cost and improve healing efficacy by providing therapeutic ES in a bandage that does not need to be repositioned for each treatment session thus improving uniformity of ES therapy. SmartMAEDS also provides innovative remote monitoring capabilities to reduce unnecessary dressing changes. By assessing wound bed impedance, SmartMAEDS will monitor progress towards healing. SmartMAEDS will also check for early indications of infection by monitoring wound bed temperature. Development of the Smart MAEDS system will include refinement of the disposable flexible substrate and the reusable stimulation/control module. Our collaborators at Koronis Biomedical Technologies will develop two software applications to manage SmartMAEDS wireless communication. StimCheck will run in the background providing instant feedback on connection status. StimMANAGE will provide a clinical user interface for real time monitoring of wound status including graphical history and trends, enabling the clinician to control and modify therapy as needed. We will evaluate SmartMAEDS in a pig model of ischemic wounds of a clinically relevant size. ES paradigms shown to enhance healing and reduce infection in our preliminary work will be assessed. Quantitative non-destructive in vivo assessment methodologies will include monitoring of tissue ischemia and progressive wound healing using transcutaneous blood gas levels and serial 3D digital photography. Wound status at fixed timepoints will be evaluated using histology, histomorphometry, immunohistochemistry and rt-PCR to determine the expression of over 80 genes involved in all stages of wound healing. Planktonic bacterial infection status, biofilm formation and microbial community profiling will also be evaluated following protocols developed in our previous work. Prototype SmartMAEDS devices have been developed under the Advanced Platform Technology Center Quality Systems/Design Control-program. A multidisciplinary clinical expert review panel will ensure that this new approach to chronic wound therapy will be highly acceptable to clinical users. The effective treatment of chronic wounds is integral to providing the highest standards of health care for Veterans. Translational pre- clinical evaluation of SmartMAEDS using a valid animal model will provide a strong foundation for effective translation to clinical care. Our collaboration with Koronis Biomedical Technologies will support pre-market development of a user-friendly bandage that can be worn for up to five days, concurrently delivering treatment and monitoring wound status. SmartMAEDS will be a disruptive value-driven technology in the wound care market at lower cost to VHA providing increased clinical benefit for Veterans with chronic wounds.